Pembrolizumab As Second-Line Therapy in Patients With Advanced Hepatocellular Carcinoma in KEYNOTE-240: A Randomized, Double-Blind, Phase III Trial

American Society of Clinical Oncology (ASCO) - Tập 38 Số 3 - Trang 193-202 - 2020
Richard S. Finn1, Baek‐Yeol Ryoo2, Philippe Merle3, Masatoshi Kudo4, Mohamed Bouattour5, Ho Yeong Lim6, В. В. Бредер7, Julien Edeline8, Yee Chao9, Sadahisa Ogasawara10, Thomas Yau11, Marcelo Garrido12, Stephen L. Chan13, Jennifer J. Knox14, Bruno Daniele15, Scot Ebbinghaus16, Erluo Chen16, Abby B. Siegel16, Andrew X. Zhu17, Ann‐Lii Cheng18
1University of California, Los Angeles, Los Angeles, CA
2Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
3Lyon North Hospital, Lyon, France
4Kindai University, Faculty of Medicine, Osaka, Japan
5Beaujon University Hospital, Assistance Publique–Hôpitaux de Paris, Clichy, France
6Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
7NN Blokhin National Medical Research Center of Oncology, Ministry of Health, Moscow, Russian Federation
8Centre Eugène Marquis, Rennes, France
9Taipei Veterans General Hospital, Taipei, Taiwan
10Chiba University Graduate School of Medicine, Chiba, Japan
11The University at Hong Kong, Hong Kong, People’s Republic of China
12Pontificia Universidad Catolica de Chile, SANTIAGO, Chile
13State Key Laboratory of Translation Oncology, Sir YK Pao Centre for Cancer, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China
14Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada
15Ospedale del Mare, Napoli, Italy
16Merck, Kenilworth, NJ
17Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA
18National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan

Tóm tắt

PURPOSE Pembrolizumab demonstrated antitumor activity and safety in the phase II KEYNOTE-224 trial in previously treated patients with advanced hepatocellular carcinoma (HCC). KEYNOTE-240 evaluated the efficacy and safety of pembrolizumab in this population. PATIENTS AND METHODS This randomized, double-blind, phase III study was conducted at 119 medical centers in 27 countries. Eligible patients with advanced HCC, previously treated with sorafenib, were randomly assigned at a two-to-one ratio to receive pembrolizumab plus best supportive care (BSC) or placebo plus BSC. Primary end points were overall survival (OS) and progression-free survival (PFS; one-sided significance thresholds, P = .0174 [final analysis] and P = .002 [first interim analysis], respectively). Safety was assessed in all patients who received ≥ 1 dose of study drug. RESULTS Between May 31, 2016, and November 23, 2017, 413 patients were randomly assigned. As of January 2, 2019, median follow-up was 13.8 months for pembrolizumab and 10.6 months for placebo. Median OS was 13.9 months (95% CI, 11.6 to 16.0 months) for pembrolizumab versus 10.6 months (95% CI, 8.3 to 13.5 months) for placebo (hazard ratio [HR], 0.781; 95% CI, 0.611 to 0.998; P = .0238). Median PFS for pembrolizumab was 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 2.5 to 4.1 months) for placebo at the first interim analysis (HR, 0.775; 95% CI, 0.609 to 0.987; P = .0186) and 3.0 months (95% CI, 2.8 to 4.1 months) versus 2.8 months (95% CI, 1.6 to 3.0 months) at final analysis (HR, 0.718; 95% CI, 0.570 to 0.904; P = .0022). Grade 3 or higher adverse events occurred in 147 (52.7%) and 62 patients (46.3%) for pembrolizumab versus placebo; those that were treatment related occurred in 52 (18.6%) and 10 patients (7.5%), respectively. No hepatitis C or B flares were identified. CONCLUSION In this study, OS and PFS did not reach statistical significance per specified criteria. The results are consistent with those of KEYNOTE-224, supporting a favorable risk-to-benefit ratio for pembrolizumab in this population.

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American Society of Clinical Oncology (ASCO)

Tập 38 Số 3

193-202

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